Year 1 Life Sciences
Epigenetics. What is it and how can we use it for good?
Epigenetics is the study of modifications and additions distributed across genome, which effect gene expression without changing the core genomic sequence of DNA (Handel et al, 2009). The NIH has set up the ‘Epigenetic Roadmap’ project which is being used to sequence Epigenetic maps which will show the variation of epigenetic tags across the genome. There has been a lot of money invested in this project as it is thought to be essential for understanding developmental, environmental and hereditary aspects of disease. Moreover the changeability of epigenetic tags has lead to interesting possibilities in the treatment and prevention of certain disease (Bernstein et al, 2010).
The aims of the ‘Epigenetic Roadmap’ project were to firstly provide a free, public recourse of mapped epigenome data for relevant disease analysis. Secondly to create innovative new technologies, in order to study epigenetic tags more efficiently. Finally, to determine the function of epigenetic tags in the genome in genetic diseases (Unknown, 2015).
The epigenome is often referred to as the secondary genome, as it directly affects the packaging the expression of genes. DNA in vivo is packaged; the DNA strand is wound around eight core histone proteins, to form a nucleosome (fig. 1). This was thought to be only because the DNA needed to be more tightly packed for storage. However recent studies have shown that this packaging affects the accessibility of the DNA, therefore impacting on whether a gene is expressed (Bernstein et al, 2010). When this packaging is modified a gene can be inhabited or activated, which can cause disease. An example of this would be, the activation of an oncogene causing cell proliferation and leading to cancer (Handel et al, 2009).
Practically all the cells in an organism have the same genetic code, but each cell is specialized to a particular function (Handel et al, 2009). This can be accounted for by DNA methylation, RNA expression and histone modification. The NIH is currently studying these aspects of epigenetics intently.
DNA methylation is the process where a methyl group, normally –CH4, is added to a sequence of DNA (Simmons, 2008). Methylation by DNA methlytranferase (DNMTs) enzymes occurs at specific CpG sites. This is where a phosphate group lies between the bases cytosine to a guanine. In the vertebrate genome sixty to ninety percent of these CpG sites are methylated (Bird, 1986). Methylation changes the composition of the DNA molecule and this can alter its interaction with transcription factors with the nucleus (Simmons, 2008).
CpG rich sequences, named HTF islands, have been studied closely to confirm their function in gene expression. These HTF islands are surprisingly not methylated like most CpG sites, due to the clustered nature of the cytosine and guanine bases. Genes with these regions are therefore constantly available to the nucleus (Bird, 1986). They are normally present on ‘housekeeping genes’, cells which are expressed in all cells, required for basic functions in normal conditions (Eisenberg & Levanon, 2013). If a HTF island is methylated then the transcription of the gene is inhibited, as it cannot reach transcriptional factors in the nucleus. This therefore leads to inhibited basic function of cells. HTF islands are also present on proto-oncogenes such as c-int 1 (Bird, 1986). The methylation of a proto-oncogene causes the establishment of an oncogene, which trigger cell proliferation and can lead to, in this case, breast cancer. The relevance of these studies are very apparent as they increase understanding of the complex human genome and can lead to plausible treatment for epigenetic diseases.
Histone modification is also widely studied in the ‘Epigenetic Roadmap’ project. Aforementioned…